The role of the immune system is critical in the control of diseases such as cancer, as well as diseases caused by external agents such as virus or bacteria. Presently, there is great interest in the use of therapeutic materials which can enhance the response of the immune system, particularly with regard to the treatment of cancer and AIDS. It has been known for some time that various bacteria manifest a strong anti-tumor and immunostimulatory effect. Also, it has been found that these bacteria can also act as an adjuvant material. An adjuvant is a material which, when introduced into an animal, along with an antigen, evokes and enhance production of antibodies to that antigen.
Various bacterial preparations have been investigated for use as immunostimulatory agents. Freund's Complete Adjuvant (CFA) was developed in the early 1950's. It comprises a crude preparation of a bacteria of the genus Mycobacterium, particularly M. tuberculosis. CFA has been found to be a relatively potent adjuvant and has become a research standard; however, its use as a therapeutic agent, and in some instances its use as a research material, has been limited by the fact that it is quite toxic. In an attempt to overcome the toxicity of CFA, various other i adjuvant materials have been developed; for example, as disclosed by Bennett et al. in "Journal of Immunological Methods" 153 (1992) 31-40, a synthetic material comprising a water in oil emulsion of squalene together with a particular block copolymer has been found to have adjuvant activity. This material is still somewhat toxic and it is employed in a non-aqueous base and hence of limited utility.
Various bacterial preparations have been developed in an attempt to improve upon CFA. As disclosed in U.S. Pat. No. 4,726,947, a relatively high molecular weight extract of various species of Mycobacterium has been found to have adjuvant and anti-tumor effects. As disclosed in U.S. Pat. No. 5,116,614, cell wall preparations of the bacterial genus Nocardia have adjuvant and anti-tumor effects when coupled with particular synthetic molecules.
All the prior art adjuvant and anti-tumor materials have been found to be less than adequate for clinical applications. The immunostimulatory effect of prior art materials is generally far less than that of CFA. Furthermore, many of these materials are toxic and difficult to prepare. Furthermore, most are not aqueous based and, hence, their use is further complicated. It will be appreciated that there is a need for an immunotherapeutic agent which is of high activity and low toxicity. The agent should also be easy to prepare and administer. The present invention provides an immunotherapeutic agent derived from bacterial cells. The agent is highly active and of low toxicity. Its preparation is relatively simple and it is a stable, aqueous based material. These and other advantages of the present invention will be readily apparent from the discussion which follows: